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Fibrosis assessment in chronic hepatitis B (CHB) is essential for prediction of long-term prognosis and proper treatment decision. This study was conducted to assess predictability of 5 simple noninvasive fibrosis indexes in comparison to liver biopsy in CHB patients.A total of 200 CHB adult Egyptian patients were consecutively included in this study, all were subjected to liver biopsy with staging of fibrosis using METAVIR scoring system. Fibrosis indexes including S-index, red cell distribution width to platelets ratio index (RPR), fibrosis-4 index (Fib-4), AST to platelets ratio index (APRI), and AST/ALT ratio index (AAR) were compared to biopsy result and their predictabilities for the different fibrosis stages were assessed using area under receiver operating characteristic curve (AUROC) analysis.S-index showed the highest AUROCs for predicting fibrosis among the studied indexes. AUROCs of S-index, RPR, Fib-4, APRI, and AAR were: 0.81, 0.67, 0.70, 0.68, and 0.60 for prediction of significant fibrosis (F2–F4), 0.90, 0.66, 0.68, 0.67, and 0.57 for advanced fibrosis (F3–F4), and 0.96, 0.62, 0.61, 0.57, and 0.53 for cirrhosis (F4), respectively. The optimal S-index cutoff for ruling in significant fibrosis was ≥0.3 with 94% specificity, 87% PPV, and 68% accuracy, while that for ruling out significant fibrosis was <0.1 with 96% sensitivity, 91% NPV, and 67% accuracy. Accuracy of S-index was higher for predicting cirrhosis (91%) than that for predicting advanced fibrosis (79%) and significant fibrosis (68%).S-index has the highest predictability for all fibrosis stages among the studied fibrosis indexes in HBeAg-negative CHB patients, with higher accuracy in cirrhosis than in the earlier fibrosis stages.